Faculty Collaboration Database

Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T-cell depletion. Biol Blood Marrow Transplant 2001;7(11):620-30

Date

01/05/2002

Pubmed ID

11760150

DOI

10.1053/bbmt.2001.v7.pm11760150

Scopus ID

2-s2.0-0034747266 (requires institutional sign-in at Scopus site)   58 Citations

Abstract

Multivariate analysis was performed to determine the independent factors affecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chronic GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-depleted (TCD) marrow allografts who received transplants at a single center between 1991 and 2000. All patients received grafts partially depleted of CD3+ T cells by complement-mediated lysis using 2 narrow-specificity monoclonal antibodies (MoAbs), T10B9.1A-31 (n = 400) or Muromonab-Orthoclone OKT3 (n = 81). Factors considered in the analysis included patient/donor sex, age, cytomegalovirus (CMV) status, and ABO blood group along with T-cell dose, disease, and disease status, donor relationship, HLA antigen (Ag)mismatch (MM), growth-factor use, anti-thymocyte globulin use, year of transplantation, and the MoAb used for TCD. The results showed an association of HLA with an increased relative risk (RR) of aGVHD for recipients of grafts from relateddonors that were > or =2 Ag MM (n = 73, RR = 2.09, P = .005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), and > or =2 Ag MM UR donors (n = 34, RR = 2.68, P = .003) compared with the baseline matched-sibling group (n = 121). No increased risk of aGVHD was seen for 0 to 1 Ag MM family donors (n = 24) or 1 Ag MM UR donors (n = 99). aGVHD risk was increased with minor, but not major or major-minor, ABO disparity (RR = 2.0, P = .003) compared with that of ABO-identical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, the use of OKT3 and not the T-cell dose was associated with increased aGVH-D risk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associated with patient age of >20 years (RR = 2.2, P < .0001) and with CMV status (positive patient/negative donor, RR = 1.9, P = .002). Decreased survival was associated with older age (>20 years), a > or =2 Ag MM related donor, a 1 or > or =2 Ag MM UR donor, risk group, and a CMV-positive patient/-negative donor pair. There was no difference in survival for 0 to 1 Ag MM related or matched UR donors compared with the baseline group. These data indicate that there are quantitative as well as potential qualitative differences in outcome depending on the TCD method. Expected and unexpected risk factors for GVHD and survival were associated with partial TCD. Our data support the consideration of ABO match in donor selection, the preferential selection of CMV-positive donors for CMV-positive recipients, and the acceptance of 1 but not > or =2 Ag HLA MM donors.

Author List

Keever-Taylor CA, Bredeson C, Loberiza FR, Casper JT, Lawton C, Rizzo D, Burns WH, Margolis DA, Vesole DH, Horowitz M, Zhang MJ, Juckett M, Drobyski WR

Authors

James Casper MD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MS, MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Colleen A. Lawton MD Emeritus Professor in the Radiation Oncology department at Medical College of Wisconsin
David A. Margolis BA, MD Chair, Professor in the Pediatrics department at Medical College of Wisconsin
J. Douglas Rizzo MS, MD Director, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Mei-Jie Zhang PhD, MS Emeritus Professor in the Data Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ABO Blood-Group System
Adolescent
Adult
Aged
Antibodies, Monoclonal
Blood Group Incompatibility
Bone Marrow Transplantation
Child
Child, Preschool
Female
Graft vs Host Disease
Histocompatibility
Histocompatibility Testing
Humans
Infant
Lymphocyte Depletion
Male
Middle Aged
Multivariate Analysis
Retrospective Studies
Risk Factors
Survival Analysis
T-Lymphocytes
Transplantation Immunology
Transplantation, Homologous